Poor glycaemic control is associated with increased risk of neurodevelopmental disorders in childhood-onset type 1 diabetes: a population-based cohort study

AIMS/HYPOTHESIS: The aim of this study was to investigate the effect of childhood-onset type 1 diabetes on the risk of subsequent neurodevelopmental disorders, and the role of glycaemic control in this association. We hypothesised that individuals with poor glycaemic control may be at a higher risk of neurodevelopmental disorders compared with the general population, as well as compared with individuals with type 1 diabetes with adequate glycaemic control. METHODS: This Swedish population-based cohort study was conducted using data from health registers from 1973 to 2013. We identified 8430 patients with childhood-onset type 1 diabetes (diagnosed before age 18 years) with a median age of diabetes onset of 9.6 (IQR 5.9–12.9) and 84,300 reference individuals from the general population, matched for sex, birth year and birth county. Cox models were used to estimate the effect of HbA(1c) on the risk of subsequent neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability. RESULTS: During a median follow-up period of 5.6 years, 398 (4.7%) individuals with type 1 diabetes received a diagnosis of any neurodevelopmental disorder compared with 3066 (3.6%) in the general population, corresponding to an adjusted HR (HR(adjusted)) of 1.31 (95% CI 1.18, 1.46) after additionally adjusting for other psychiatric morbidity prior to inclusion, parental psychiatric morbidity and parental highest education level. The risk of any neurodevelopmental disorder increased with HbA(1c) levels and the highest risk was observed in patients with mean HbA(1c) >8.6% (>70 mmol/mol) (HR(adjusted) 1.90 [95% CI 1.51, 2.37]) compared with reference individuals without type 1 diabetes. In addition, when compared with patients with diabetes with HbA(1c) <7.5% (<58 mmol/mol), patients with HbA(1c) >8.6% (>70 mmol/mol) had the highest risk of any neurodevelopmental disorder (HR(adjusted) 3.71 [95% CI 2.75, 5.02]) and of specific neurodevelopmental disorders including ADHD (HR(adjusted) 4.16 [95% CI 2.92, 5.94]), ASD (HR(adjusted) 2.84 [95% CI 1.52, 5.28]) and intellectual disability (HR(adjusted) 3.93 [95% CI 1.38, 11.22]). CONCLUSIONS/INTERPRETATION: Childhood-onset type 1 diabetes is associated with an increased risk of neurodevelopmental disorders, with the highest risk seen in individuals with poor glycaemic control. Routine neurodevelopmental follow-up visits should be considered in type 1 diabetes, especially in patients with poor glycaemic control. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-020-05372-5.